Oncosphere

Oncospheres of many cestode species penetrate and develop into metacestodes within cysts (cysticerci, hydatid, multilocular) in the soft tissues of their rodent, ruminant or human hosts. Thus, species such as Echinococcus granulosus, E. multilocularis, Eaenia multiceps, T. ovis, E. saginata and E solium are of economic and medical importance. Such soft tissue invasion elicits a host immune response to resist the helminths. However, although some cysts may be destroyed as evidenced by involution or calcification, the host response is often too little - too late to eliminate the invaders. The susceptibility of the host to invasion is often due to successful evasive strategies... 

Although sheep are not well protected against T. ovis oncospheral invasion by passive transfer of AB in colostrum, mice were protected against T. taeniaeformis by the oral administration of colostral IgA and IgG (Lloyd and Soulsby, 1 978) or serum IgG (Musoke and Williams, 1975) from infected animals. 

In murine E. granulosus oncospheral infections, the primary AB response associated with protection against a re-infection was lgG1 (Zhang et al., 2003). Elevated lgG1 is associated with Th2 reactions, yet most tissue invasive cestodes seem to produce an initial Th1 or mixed Th1/Th2 response (Cortes et al., 2003 Vuitton, 2003). 

Immunization with the monoclonal AB reactive against the 18 kDa major surface protein in the oncosphere of T. saginata, HP6, confers protection in cattle (Harrison and Rarkhouse, 1986). The HP6-encoding gene of T. saginata has been cloned and transfected into normal rat kidney cells. Localization studies revealed HP6 in the endoplasmic reticulum, the Golgi apparatus and at the cell surface (Bonay et al., 2002). The deduced amino acid sequence of HP6 was similar to the mammalian extracellular matrix protein,... 

Benitez, L., Carate, T., Harrison, L.J., Kirkham, P., Brookes, S.M. and Rarkhouse, R.M. (1996) Cloning and sequencing of the gene encoding the principal 18-kDa secreted antigen of activated oncospheres of Taenia saginata. Molecular and Biochemical Parasitology 78, 265-268. 

Bogh, H.O., Lightowlers, M.W, Sullivan, N.D., Mitchell, C.F. and Rickard, M.D. (1990) Stage-specific immunity to Taenia taeniaeformis infection in mice. A histological study of the course of infection in mice vaccinated with either oncosphere or metacestode antigens. Parasite Immunology 12, 1 53-1 62. 

Harrison, L.J. and Parkhouse, R.M. (1 986) Passive protection against Taenia saginata infection in cattle by a mouse monoclonal antibody reactive with the surface of the invasive oncosphere. Parasite Immunology 8, 319-332. 

Heath, D.D. and Pavloff, P. (1975) The fate of Taenia taeniaeformis oncospheres in normal and passively protected rats. International Journal for Parasitology 5, 83-88. 

Predicted Protein Structure and Function of Oncosphere Antigens.293... 

Taeniid cestodes have a prey-predator life cycle involving two mammalian hosts. The definitive host is a carnivore or omnivore, which harbours the adult tapeworm parasite in the small intestine. Mature infective eggs are released with the faeces and, when these are ingested by a suitable species of intermediate host, the oncosphere contained within the egg is liberated through the influence of intestinal secretions, particularly bile. The activated parasite penetrates the mucosa of the small intestine... 

Table 15.2. Recombinant oncosphere antigens of taeniid cestodes, which have been shown to induce host-protective immune responses. ...

The discovery that oncosphere extracts provided a source of potent, protective antigens for both Taenia species and E. granulosus raised the potential for development of practical vaccines to prevent infections with economic and... 

Early studies with T. taeniaeformis in mice (Miller and Gardiner, 1932 Campbell, 1938b Leid and Williams, 1974 Musoke et al., 1975 Mitchell et al., 1977, 1980), T. pisiformis in rabbits (Campbell, 1938a), T. saginata in cattle (Lloyd and Soulsby, 1976) and T. ovis in sheep (Blundell et al., 1968 Rickard et al., 1977 Heath et al., 1979 Harrison et al., 1993) demonstrated that antibodies in the sera of infected or immunized hosts were capable of transferring passive immunity to na ive hosts. The presence and activities of these protective antibodies were found to be evident in vitro through the demonstration that activated oncospheres were killed if cultured in the presence of serum from infected or vaccinated... 

The native oncosphere proteins corresponding to both To45W and EG95 are substantially larger than would be predicted by their protein sequences (Johnson et al., 1989 Lightowlers et al., 1996a), and both proteins... 

All of the oncosphere antigens cloned to date contain either one of two copies of a predicted Fnlll domain. These domains are widely distributed in eukaryotic proteins and occur also in some prokaryotic proteins (Bork and Doolittle, 1992). Approximately 2% of animal proteins include Fnlll domains. Many, but not all, of these proteins are extracellular and some have roles as adhesins. The structure of this 100 amino acid domain is highly conserved and consists of two layers with three p strands in one plane and four p strands in another (Potts and Campbell, 1996). Overall, amino acid sequence identity between different Fnlll domains is low, even between Fnlll repeat domains within fibronectin itself (Plaxco et al., 1997). Nevertheless, certain residues are highly conserved and maintain the tertiary structure of the proteins (Bork and Doolittle, 1992). Other conserved motifs such as an Arg-Gly-Asp (RGD) motif within a loop of some Fnlll domains is associated with proteins having cell adhesion properties, as discussed above (Ruoslahti and Pierschbacher, 1987 D Souza et al., 1991). 

There are many features of the genes encoding oncosphere proteins that are common amongst the genes from different taeniid species. The structure of the genes encoding the various... 

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